Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.
Cell. 2010 Feb 5;140(3):421-35. doi: 10.1016/j.cell.2010.01.008.
Prions are proteins that can assume at least two distinct conformational states, one of which is dominant and self-perpetuating. Previously we found that a translation regulator CPEB from Aplysia, ApCPEB, that stabilizes activity-dependent changes in synaptic efficacy can display prion-like properties in yeast. Here we find that, when exogenously expressed in sensory neurons, ApCPEB can form an amyloidogenic self-sustaining multimer, consistent with it being a prion-like protein. In addition, we find that conversion of both the exogenous and the endogenous ApCPEB to the multimeric state is enhanced by the neurotransmitter serotonin and that an antibody that recognizes preferentially the multimeric ApCPEB blocks persistence of synaptic facilitation. These results are consistent with the idea that ApCPEB can act as a self-sustaining prion-like protein in the nervous system and thereby might allow the activity-dependent change in synaptic efficacy to persist for long periods of time.
朊病毒是能够呈现至少两种不同构象状态的蛋白质，其中一种状态占主导地位且自我维持。先前我们发现，来自海兔的一种翻译调节剂 CPEB（Aplysia CPEB，ApCPEB）可以稳定突触效能的依赖活动变化，它在酵母中表现出类朊病毒特性。在这里，我们发现 ApCPEB 在外源表达于感觉神经元时，可以形成淀粉样的自我维持多聚体，这与它是类朊病毒蛋白一致。此外，我们发现，外源性和内源性 ApCPEB 向多聚体状态的转化都被神经递质血清素增强，并且优先识别多聚体 ApCPEB 的抗体可以阻止突触易化的持续。这些结果与 ApCPEB 可以在神经系统中充当自我维持的类朊病毒蛋白的观点一致，从而可能允许突触效能的依赖活动变化持续很长时间。
